Breast Cancer Metastasis Controlling Genes

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

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3.1. Metastasis-Promoting Genes (MPGs)

These are the proteins that are implicated to influence critical steps in the metastasis of breast cancer resulting in promotion of metastasis. These critical steps and the genes involved are summarized in Table 1.

3.1.1. Immune evasion

Cancer cells can grow by escaping from the attack of immune cells, thus disrupting the host immune system, which is progressively suppressed as a result of tumor progression and metastasis. The molecular mechanisms by which cancer cells evade the host immune system have been investigated in mouse models and clinical samples.

Tumor cells employ several mechanisms to evade immune response including loss of tumor antigen, alteration of HLA class I antigen, defective death receptor signaling, lack of costimulation, immunosuppressive cytokines, and immunosuppressive T cells (9). Gutierrez et al. showed that FasL expression by breast tumor plays a central role in the induction of apoptosis of infiltrating Fas-immune cells providing a mechanism for tumor immune privilege (10). It was also observed that FasL in breast tissue is functionally active and that tamoxifen inhibits FasL expression, allowing the killing of cancer cells by activated lymphocytes (11). Fas exists in two forms, transmembrane and soluble (sFas). A study by Bewick et al. suggests that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome for patients with metastatic breast cancer undergoing high-dose chemotherapy (12). sFas induces host lymphocyte apoptosis and impairs expression of NKG2D and T-cell activation. A study by Ueno et al. reports that compared with healthy female controls, breast cancer patients, especially those with liver metastases, have higher circulating sFas levels (13).

Table 1. Critical steps and genes involved in breast cancer metastasis

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